The invention relates to methods and devices for the gas-assisted transport of ions from an ion source outside the vacuum into the vacuum system of an ion user, such as a mass spectrometer. In modern mass spectrometers the ions are often generated at atmospheric pressure (API=atmospheric pressure ionization) outside the mass spectrometer. The best known and most prevalent source of this kind is the electrospray ion source (ESI), which can mainly be used for polar substances such as proteins, but ion sources using chemical ionization at atmospheric pressure (APCI) or photoionization at atmospheric pressure (APPI) are increasingly used. Laser ionization of gaseous molecules at atmospheric pressure (APLI) was added recently, and matrix-assisted laser ionization of solid samples on sample supports can also be performed at atmospheric pressure (AP-MALDI).
In mass spectrometers with atmospheric pressure ion sources, the ions first have to be transferred into the vacuum and then transported to the mass analyzer through a number of differential pump stages. Very efficient systems such as RF ion funnels and RF ion guides are available to transport the ions within the vacuum system, but they only work well in vacua at pressures below a few hectopascal. To transfer the ions from atmospheric pressure into the vacuum system of the mass spectrometer, many commercial mass spectrometers nowadays use long inlet capillaries which introduce the gas directly into the first stage of the vacuum system, following the invention of the Nobel Laureate John B. Fenn and his colleagues. If one considers the transport efficiency along the whole transport path of the ions from their generation in the ion source to the analysis in the ion analyzer, however, the inlet capillary is the weakest link in the chain by far. Firstly, the inlet capillary limits the amount of gas introduced, and thus also the quantity of ions introduced with the gas; secondly, the transport of the ions through the inlet capillary is associated with an ion loss of 80 to 90 percent.
Other commercial mass spectrometers use conical apertures, which do not usually lead directly into the first vacuum stage, but initially into a prevacuum stage. One example is the Z-Spray™ from Waters, (S. Bajic, U.S. Pat. No. 5,756,994), which represents such a dual-step introduction of the ions via two successive, conical entrance orifices positioned perpendicularly to each other with appropriately applied electric suction voltages. From the prevacuum stage the ions are transferred through the second conical orifice into the first vacuum stage of the mass spectrometer. The sensitivity of these mass spectrometers is no higher than that of the mass spectrometers with inlet capillaries, however, and one must therefore assume that high ion losses occur here, too.
In air or other gases, ions can survive for any length of time if their ionization energy is less than the ionization energy of the ambient gas molecules, if neither ions of the opposite polarity nor electrons are available for recombination, and if no collisions with walls can take place which would regularly discharge the ions and thus destroy them as ions.
Ions can be transported through gases by means of electric fields, in which case the laws of ion mobility apply, according to which the ions move at a relatively slow speed along the electric lines of force, being continuously retarded by friction with the gas and their direction being only slightly affected by diffusion. It is, however, also possible to transport the ions by means of the moving ambient gas itself if the ambient gas has a pressure at which the ions can be viscously entrained. If ion-containing gas is pressed through a tube or capillary, for example, ions are entrained in the gas and transported through the tube or capillary. The best known example is the above-mentioned inlet capillary into the vacuum of a mass spectrometer.
It is known from capillary chromatography that all molecules of a gas moving through a capillary suffer an extraordinarily high number of wall collisions. The number of wall collisions essentially corresponds to the number of theoretical (vaporization) plates which represent the separation efficiency of chromatographic columns. In capillary columns this is extremely high. A rough rule of thumb for an optimal gas velocity (the “van Deemter velocity”) is that a molecule statistically collides once with the wall after a path which corresponds to the diameter of the capillary. For higher gas speeds, the number of wall collisions per unit of path length decreases. Time and again, however, a molecule under consideration covers long paths with no wall collisions interspersed with paths with much more frequent wall collisions. It follows that only those ions which happen to cover a long path without coming into contact with the wall can get through a capillary undamaged. It may be assumed that these ions have entered the capillary roughly in the center.
The phenomenon of ion transport in capillaries was investigated in the paper “Ion Transport by Viscous Gas Flow through Capillaries” by B. Lin and J. Sunner in J. Amer. Soc. Mass Spectr. 5, 873 (1994). The authors first refuted the widely held view that the ions can be pushed to the center of the capillary by applying a charge to the capillary walls. Inside a capillary with uniformly charged walls there is a field-free drift region with no focusing properties. The ions experience no repulsion whatsoever when they approach the charged wall. The authors' experiments showed that the diffusion of the ions toward the walls does indeed cause high losses to the extent which was theoretically to be expected and that, as was statistically to be expected, only a residual number of the ions can pass undamaged through the capillary. The relative yield of transported ions decreases with the length of the capillary, and there is a similar drastic reduction for thinner capillaries. A further loss occurs because of space charge effects at high ion density; the Coulomb repulsion drives the ions to the capillary walls. The space charge effects limit the absolute yield of ions during transport through such inlet capillaries.
The paper “Improved Ion Transmission from Atmospheric Pressure to High Vacuum Using a Multicapillary Inlet and Electrodynamic Ion Funnel Interface” by T. Kim et al., Anal. Chem, 72, 5014-5019 (2000) describes how a bundle of seven similar metal capillaries, soldered into a block, can achieve much more than seven times the ion transport of a single metal capillary with similar dimension, although the seven capillaries have to be equipped with a more powerful pump system in order to achieve roughly the same pressure in a downstream ion funnel. How the bundle of seven capillaries achieves the 10- to 20-fold ion transport is still unexplained. Nor is there an explanation as yet as to how two different bundles whose individual capillaries have inside diameters of 0.51 and 0.43 millimeters respectively, whose gas streams must differ mathematically by a factor of two in accordance with Hagen-Poiseuille, demonstrated a reduction of the ion transport of only 30 percent.
It can only be surmised that mutual influencing of the gas streams means that the inflow of the ions into the seven adjacent capillaries of the bundle is more organized than the inflow into a single capillary, and possibly leads to less turbulence in the inlet region of the capillary. That the organization of the gas at the capillary inlet is important is shown in the following paper: “Improved Capillary Inlet Tube Interface for Mass Spectrometry—Aerodynamic Effects to Improve Ion Transmission”, D. Prior et al., Computing and Information Sciences 1999 Annual Report. The authors report that a slight funnel-shaped widening of the capillary inlet leads to a fourfold increase in the transmission of ions from an electrospray ion source. These findings could not be confirmed by other working groups, possibly because more ideal conditions already prevailed in their initial set-up.
The gas load in the vacuum system of a mass spectrometer generally makes it necessary to have a differential pumping system with at least three pressure stages. Commercially available electrospray devices incorporate at least three, usually even four pressure stages. There are now four-stage turbomolecular pumps designed especially for these applications commercially available. In the first differential pumping stage there is a relatively high pressure, usually in the region of several hectopascals up to a maximum of several kilopascals; such a high pressure greatly impedes the onward transmission of the ions. The pressure in this differential pumping stage determines the upper limit for the inflow of gas and limits the dimensions of the inlet capillaries used.
As the gas flows out of the inlet capillary, a weakly focused gas jet forms in the first pump stage, said jet usually being directed at the small aperture to the next pump stage. Located around the aperture is a conical gas skimmer which repels the gas in the outer part of the gas jet toward the outside. The skimmer usually has an electric potential intended to guide the ions through the aperture. This results in high focusing and scattering losses, however.
A recent trend is to use RF ion funnels instead of the skimmers. Ion funnels consist of a series of diaphragms with round apertures whose diameters become progressively smaller so that a funnel-shaped space is created in the interior. The last diaphragm, with the smallest aperture diameter, usually represents the transition to the next vacuum chamber. The two phases of an RF voltage are applied in turn to the diaphragms, generating a pseudopotential which keeps the ions away from the diaphragm edges forming the wall of this funnel. A DC voltage superimposed on the diaphragms generates an axial DC field, which guides the ions to the exit of the funnel at the narrow end. The use of these funnels improves the ion transport through this first pressure stage, but is limited to pressures below a few kilopascals, preferably below a few hectopascals, because otherwise the pseudopotentials of the ion funnel are no longer able to repel the ions, on the one hand, and because the ions are transported in the direction opposing the pseudopotential viscously entrained by the gas emerging between the diaphragms, on the other hand. In the second pressure stage it is then possible to capture the ions effectively by using an ion guide made of a multipole arrangement with long pole rods, for example, or by employing a second ion funnel.
With the prior art it is only possible to transport a small proportion of the ions from a large ion cloud into the vacuum undamaged. However, it has so far proven impossible to find really consistent data on what percentage of the ions flowing into an inlet capillary pass through undamaged. Most sources give a figure in the single digit percentage range; maximum estimates are around 20 percent. There is much room for improvement here. Moreover, in conventional atmospheric pressure ion sources, only a small proportion of the ions generated are actually introduced into the inlet capillary by the gas; here, too, improvements are possible.